Human papillomavirus (HPV) causes common, but usually transient, infections of the cervix that sometimes become cervical cancer. Since few of the women infected with HPV get cervical cancer, we are interested in cofactors in addition to HPV that promote tumor formation. One such possible cofactor is Chlamydia trachomatis, a prevalent, sexually transmitted disease that can infect the cervix for long periods of time. A recent article suggested that specific serotypes of C. trachomatis were associated with the development of cervical squamous cell cancer. We have a population based sample of 500 cervical cancer cases and 300 controls blood samples that have been tested for antibodies to HPV and have been interviewed for risk factors for cervical cancer. The tumor tissue has been tested for HPV DNA by polymerase chain reaction. This resource will allow us to quickly and efficiently test for C. trachomatis in order to evaluate two hypotheses. First, whether an increased risk of cervical carcinoma is associated with C. trachomatis, with an emphasis on the relative risks associated with the three genital C. trachomatis serotype classes. Second, to examine this association separately among women with the two main histologic types of cervical cancer, squamous cell carcinoma (n=300) and adenocarcinoma (n=200) of the cervix. Control subjects selected for this study have serum antibodies to HPV-16 or -18. The benefit of screening and treatment for chlamydial infections might extend to include prevention of the proportion of cervical cancer promoted by infection with specific serotypes of C. trachomatis. If we are able to confirm the relationship between C. trachomatis and cervical cancer, repeated targeted screening of young women for C. trachomatis may become a higher public health priority. Furthermore, our results would help determine whether further follow up of the C. trachomatis and cervical cancer association is warranted in a more expensive, prospective setting.